Nucleobindin 2 inhibits senescence in gastric carcinoma.

Here, we focused on the role of Nucleobindin 2 (NUCB2), a multifunctional protein, in gastric carcinoma (GC) progression. NUCB2 expression was investigated in 150 GC cases (20 non-invasive (pT1) and 130 invasive (pT2/pT3/pT4) tumors) by immunohistochemistry (IHC), and in situ hybridization for detection of the mRNA in 21 cases. Using GC cell lines, we determined whether NUCB2 expression was associated with specific cellular phenotypes. In GC clinical samples, NUCB2 was transcriptionally upregulated when compared to normal tissues. High NUCB2 expression was associated with clinicopathological factors including deep tumor invasion, lymphovascular invasion, lymph node metastasis, and advanced clinical stages, and was a significant independent predictor of unfavorable progression-free survival in 150 non-invasive and invasive GC patients. Similar findings were also evident in 72 invasive GC cases in which patients received post-operative chemotherapy, but not in 58 invasive tumors from patients who did not receive the chemotherapy. In cell lines, NUCB2 knockout inhibited proliferation, susceptibility to apoptosis, and migration capability by inducting cellular senescence; this was consistent with higher proliferation and apoptotic indices in the NUCB2 IHC-high compared to NUCB2 IHC-low GC cases. NUCB2-dependent inhibition of senescence in GC engenders aggressive tumor behavior by modulating proliferation, apoptosis, and migration.

Risk factors for recurrence of frozen shoulder after shoulder manipulation under ultrasound-guided cervical nerve root block.

Background: This study aimed to investigate risk factors for recurrence of frozen shoulder after shoulder manipulation under ultrasound-guided cervical nerve root block (MUC). Methods: We retrospectively reviewed 135 frozen shoulders in 121 patients who underwent MUC. We defined frozen shoulder as a limited shoulder range of motion (ROM) (passive forward flexion <120°, external rotation <30°, or internal rotation lower than L3). Patients fulfilling any one criteria were considered to have frozen shoulder. If patients continued to have severe pain and limited ROM at 3 months after MUC, we defined as recurrence of frozen shoulder and they were offered a further MUC or arthroscopic capsular release (ACR). We compared the ROM, Constant Shoulder (CS) score, and University of California, Los Angeles score before and 3 months after MUC between patients with the successful of MUC group (Success group) with those recurrence of frozen shoulder who required a further MUC or ACR group (Recurrence group). Multiple logistic regression analysis was used to identify risk factors for recurrence of frozen shoulder after MUC. Results: Patients who underwent MUC were retrospectively enrolled and divided into: the successful of MUC group (Success group, n = 112) and required a further MUC or ACR group (Recurrence group, n = 9). The Recurrence group had significantly lower external rotation and CS score before MUC than those in the Success group (P < .05). The Recurrence group showed significantly inferior all ROM and functional scores 3 months after MUC (P < .05). The levels of blood glucose and hemoglobin A1c both before and 3 months after MUC in the Recurrence group showed inferior compared with those of Success group. The difference, although not statistically significant, trended towards significance (before MUC/3 months after MUC; the glucose levels P = .06/.06, the hemoglobin A1c levels P = .07/.09, respectively). The visual analog scale pain score (at rest, during activity, at night) both before and 3 months after MUC in the Recurrence group showed significantly higher scores compared with those of Success group (P < .05). Multiple logistic regression analysis revealed that lower CS score before MUC was independent risk factor for recurrence of frozen shoulder after MUC. Conclusion: The overall incidence of recurrence of frozen shoulder after MUC was 7.4%. The lower CS score before MUC was an independent risk factor for recurrence of frozen shoulder after MUC. Moreover, patients in the Recurrence group tended to have poorly controlled diabetes and higher visual analog scale pain score both before and 3 months after MUC.

Early Postoperative Stiffness After Arthroscopic Rotator Cuff Repair Correlates With Improved Tendon Healing.

PURPOSE: To assess whether early postoperative stiffness predicts long-term stiffness and its relationship with repair integrity in patients who undergo arthroscopic rotator cuff repair (ARCR). METHODS: This was a single-center retrospective study; 427 patients undergoing primary ARCR by a board-certified orthopaedic surgeon over 4 years were considered. Patients with at least 1 year of follow-up were categorized into stiff and non-stiff groups based on their range of motion (ROM) at 3 months' postoperatively. Stiffness was defined as passive forward flexion <120°, external rotation <30°, or internal rotation below L3. We evaluated clinical outcomes using demographics, ROM, Constant Shoulder (CS) score, University of California, Los Angeles (UCLA) score, and visual analog scale (VAS) for pain preoperatively and at 3, 6, and 12 months' postoperatively. Stiffness, retear rates, and tendon integrity were assessed via magnetic resonance imaging at 12 months. RESULTS: Of 155 patients meeting the inclusion criteria, 68 (43.9%) were stiff, and 87 (56.1%) were non-stiff. The stiff group had significantly lower preoperative CS and UCLA scores (P = .013/.014) and greater VAS score (P = .034). At 3 months, this group showed lower ROM and functional scores (P < .001), persisting at 6 and 12 months (except internal rotation) (P < .001). Their 12-month VAS score was greater (P = .024). Postoperative stiffness occurred in 10.3% of the stiff group and 2.3% of the non-stiff group (P = .035). The 12-month retear rate was 5.9% in the stiff group and 17.2% in the non-stiff group (P = .032). Minimal clinically important difference analysis indicated ROM changes but limited functional score changes in the 2 groups. CONCLUSIONS: This study showed that early postoperative shoulder stiffness correlates with lower preoperative functional scores and greater pain levels. Shoulder stiffness at 3 months' post-ARCR predicts 12-month shoulder stiffness but indicates better tendon integrity. While early stiffness is linked to lower functional scores and more pain, its long-term clinical impact seems limited. LEVEL OF EVIDENCE: Level III, retrospective comparison study.

Factors affecting stress shielding and osteolysis after reverse shoulder arthroplasty: A multicenter study in a Japanese population.

BACKGROUND: Stress shielding and osteolysis around the humeral stem after reverse shoulder arthroplasty causes loosening and periprosthetic fractures and reduces bone stock during revision surgery. In Japanese patients, who have relatively small bodies, different characteristics may exist regarding the occurrence of these changes compared with the characteristics of Westerners, who have relatively larger frames. The purpose of this multicenter study was to investigate the incidence and clarify the predictors of stress shielding and osteolysis in Japanese individuals who underwent reverse shoulder arthroplasty. METHODS: The occurrence of stress shielding and osteolysis was investigated in 135 shoulders that had undergone reverse shoulder arthroplasty at least 2 years prior in five Japanese hospitals. During post-surgical follow-up, which was conducted every 3 months, the locations of the stress shielding occurrences, such as cortical thinning and osteopenia (which primarily occurred in zones 1, 2, and 7, where 1 is the greater tuberosity and 7 is the calcar part), spot weld, and condensation lines, were recorded. Cases without any abnormal findings on radiographs obtained up to ≥2 years after surgery were regarded as having no abnormalities. Finally, the predictors of cortical thinning and proximal humeral osteolysis were assessed using univariate and multivariate regression analyses. RESULTS: Cortical thinning and osteopenia occurred in 68 shoulders, a condensation line occurred in 37 shoulders, and spot weld occurred in 23 shoulders. In particular, greater tuberosity and calcar osteolysis occurred in 40 and 47 shoulders, respectively. Long stem, cementless stem, and a larger proximal filling ratio were independent predictors of cortical thinning and osteopenia, whereas a cementless stem, larger metaphysis diameter, and a larger proximal filling ratio were associated with proximal humeral osteolysis. CONCLUSIONS: The predictors of stress shielding and osteolysis included the use of long stems, cementless stems, larger proximal filling ratios, and larger metaphysis diameters. LEVEL OF EVIDENCE: retrospective comparative study (Level III).

A Complex Interplay between Notch Effectors and ß-Catenin Signaling in Morular Differentiation of Endometrial Carcinoma Cells.

Notch signaling contributes to tissue development and homeostasis, but little is known about its role in morular differentiation of endometrial carcinoma (Em Ca) cells. The current study focused on crosstalk between Notch and ß-catenin signaling in Em Ca with morules. Promoters of hairy and enhancer of split 1 (Hes1) and mastermind-like 2 (MAML2) were activated by Notch intracellular domain 1 but not ß-catenin, and a positive feedback loop between Hes1 and MAML2 was observed. Immunoreactivities for nuclear ß-catenin, Hes1, and MAML2, as well as the interaction between ß-catenin and Hes1 or MAML2, were significantly higher in morular lesions compared with surrounding carcinoma in Em Ca. Inhibition of glycogen synthase kinase-3ß (GSK-3ß) increased expression of total nuclear and cytoplasmic GSK-3ß and its phosphorylated forms, as well as Notch intracellular domain 1, Hes1, and active ß-catenin. GSK-3ß inhibition also decreased proliferation and migration, consistent with the response of cells stably overexpressing Hes1. Finally, the nuclear/cytoplasmic GSK-3ß score was significantly higher in morules compared with surrounding carcinoma in Em Ca, and it was positively correlated with nuclear ß-catenin, Hes1, and MAML2 scores. This complex interplay between Notch effectors and ß-catenin signaling through GSK-3ß inhibition contributes to the establishment and maintenance of ß-catenin-mediated morular differentiation, which is, in turn, associated with reduced proliferation and inhibition of migration in Em Ca.

Bone marrow edema in the acromioclavicular joint after arthroscopic rotator cuff repair.

BACKGROUND: Bone marrow edema (BME) in the acromioclavicular joint (ACj) may occur after arthroscopic rotator cuff repair (ARCR), resulting in persistent postoperative ACj pain. We investigated the incidence and clinical characteristics of BME in ACj after ARCR. METHODS: Patients exhibiting ACj-related symptoms prior to ARCR surgery, no BME in the ACj on MRI, and an ability to undergo 2-year postoperative physical and MRI examinations of the ACj were included. Patients who underwent distal clavicle resection or osteophyte resection below the ACj and those unable to achieve primary repair of the rotator cuff were excluded. MRI evaluation was performed preoperatively and at 3, 6, 12, and 24 months postoperatively. Patients who showed BME in ACj on fat-suppressed T2 MRI at 24 months postoperatively were classified into the BME + group, and those with no BME were classified into the BME- group. Patient background, operation time, Japanese Orthopedic Association (JOA) score, re-tear rate, ACj tenderness, and cross-body adduction test were compared between groups. In addition, we examined the time of occurrence of BME. RESULTS: A total of 345 ARCRs were performed during the study period. After the exclusion of 114 shoulders, the remaining 231 shoulders were included in this study. There were 208 cases in the BME- group and 23 cases in the BME + group. The incidence of BME was 9.96 %. Although the JOA scores of both groups showed a significant improvement postoperatively compared to preoperatively, there was no significant difference between the two groups. In terms of re-tear, there was 1 case in the BME + group and 7 in the BME- group. Positive ACj tenderness and cross-body adduction test were significantly higher in the BME + group (P < 0.001). BME occurred in 6 cases at 3 months, 9 cases at 6 months, and 8 cases at 1 year postoperatively. None of the patients developed BME at more than 1 year postoperatively. BME was observed on MRI in all cases at 2 years postoperatively. CONCLUSIONS: The rate of occurrence of BME in the ACj after ARCR was 9.96 %. Patients with BME were significantly more likely to have ACj tenderness and positive cross-body adduction test. BME in the ACj often occurs within 6 months to 1 year after ARCR of small-to-medium rotator cuff tears, suggesting a relationship with postoperative functional improvement of the shoulder joint. The ACj should be considered as a potential site of persistent pain after ARCR for small-to-medium rotator cuff tears.

Pregnancy in Seronegative Myasthenia Gravis: A Single-Center Case Series.

INTRODUCTION: The course of double-seronegative myasthenia gravis (DSNMG) during and after pregnancy has not been well described. OBJECTIVE: To assess the course of DSNMG during pregnancy and within 6 months postpartum. METHODS: A retrospective cohort study of women with DSNMG seen in the Duke Myasthenia gravis (MG) Clinic after 2003. RESULTS: Review of the Duke MG Clinic Registry and electronic medical record identified 8 patients who became pregnant after MG onset; the mean age at disease onset was 17.6 (SD = 10.0) years. Increased MG symptoms were observed in the first and third trimester and, most commonly, postpartum in 6 of 18 pregnancies. Except for 1 infant who developed respiratory distress that required neonatal intensive care admission, all the newborns were healthy at birth. CONCLUSIONS: As in seropositive MG, increased MG symptoms during pregnancy and within 6 months postpartum is also seen in women with DSNMG.

Tranexamic acid has no effect on postoperative pain control after arthroscopic rotator cuff repair: A prospective, double-blind, randomized controlled trial.

Background: The purpose of this study was to compare the efficacies of tranexamic acid (TXA) versus placebo after arthroscopic rotator cuff repair (ARCR). Methods: This prospective, double-blind, and randomized study was conducted in 70 patients who underwent ARCR from 2021 to 2022 at our hospital. Thirty-four shoulders were randomly assigned to the TXA group, and 36 to the control group; TXA (10 mL) and normal saline (10 mL) were administered locally after surgery and in the control group, respectively. We evaluated visual analog scale pain scores at rest, during activity, and at night and the circumference and diameter of the shoulder joint in both groups preoperatively and at 1, 2, and 3 days, and 1 week after the surgery. We compared and analyzed the results between the groups. Statistical significance was set at a p-value of <0.05. Results: There was no significant difference in the visual analog scale scores at rest, during activity, and at night between the groups (p > 0.05). The circumference and diameter of the shoulder joint were not also significantly different between both groups (p > 0.05). Conclusion: Local TXA administration in patients who undergo ARCR does not significantly impact postoperative pain levels and the circumference and diameter of the shoulder joint.

Interaction between membranous EBP50 and myosin 9 as a favorable prognostic factor in ovarian clear cell carcinoma.

Ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is a scaffold protein that is required for epithelial polarity. Knockout (KO) of membranous EBP50 (Me-EBP50) in ovarian clear cell carcinoma (OCCC) cells induced an epithelial-mesenchymal transition (EMT)-like phenotype, along with decreased proliferation, accelerated migration capability, and induction of cancer stem cell (CSC)-like properties. Shotgun proteomics analysis of proteins that co-immunoprecipitated with EBP50 revealed that Me-EBP50 strongly interacts with myosin 9 (MYH9). Specific inhibition of MYH9 with blebbistatin phenocopied Me-EBP50 KO, and blebbistatin treatment potentiated the effects of Me-EBP50 KO. In OCCC cells from clinical samples, Me-EBP50 and MYH9 were co-localized at the apical plasma membrane. Patients with a combination of Me-EBP50-high and MYH9-high scores had the best prognosis for overall and progression-free survival. Our data suggest that Me-EBP50 has tumor-suppressive effects through the establishment and maintenance of epithelial polarization. By contrast, loss of Me-EBP50 expression induces EMT-like phenotypes, probably due to MYH9 dysfunction; this results in increased cell mobility and enhanced CSC-like properties, which in turn promote OCCC progression.

Preemptive middle glenohumeral ligament release in arthroscopic rotator cuff repair does not reduce the postoperative stiffness: a retrospective comparative study.

BACKGROUND: This study aimed to evaluate the efficacy of preemptive middle glenohumeral ligament (MGHL) release in arthroscopic rotator cuff repair (ARCR) to reduce postoperative stiffness. METHODS: Patients who underwent ARCR were enrolled and allocated into two groups retrospectively: the preemptive MGHL release group (n = 44) and the preemptive MGHL non-release group (n = 42). Clinical outcomes were assessed and compared between the two groups, including the range of motion, Japanese Orthopedic Association Shoulder Score, Constant Shoulder Score, and the University of California, Los Angeles Score preoperatively and 3 months, 6 months, and 12 months postoperatively and complications. The integrity of the repaired tendon was assessed at the 12-month follow-up using magnetic resonance imaging. RESULTS: There were no significant differences between the groups in all range of motion and all functional scores at any of the assessed time points. There was also no significant difference in the healing failure rate 2.3% in the preemptive MGHL group and 2.4% in the preemptive MGHL non-release group (p = .97), and postoperative stiffness was 2.3% in the preemptive MGHL group and 7.1% in the preemptive MGHL non-release group (p = .28). There was no postoperative instability in both group. CONCLUSION: ARCR effectively facilitates the recovery of range of motion and function in patients with a rotator cuff tear. However, preemptive MGHL release could not be an effective method to reduce postoperative stiffness.

Inhibition of the bone morphogenetic protein pathway suppresses tumor growth through downregulation of epidermal growth factor receptor in MEK/ERK-dependent colorectal cancer.

The bone morphogenetic protein (BMP) pathway promotes differentiation and induces apoptosis in normal colorectal epithelial cells. However, its role in colorectal cancer (CRC) is controversial, where it can act as context-dependent tumor promoter or tumor suppressor. Here we have found that CRC cells reside in a BMP-rich environment based on curation of two publicly available RNA-sequencing databases. Suppression of BMP using a specific BMP inhibitor, LDN193189, suppresses the growth of select CRC organoids. Colorectal cancer organoids treated with LDN193189 showed a decrease in epidermal growth factor receptor, which was mediated by protein degradation induced by leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) expression. Among 18 molecularly characterized CRC organoids, suppression of growth by BMP inhibition correlated with induction of LRIG1 gene expression. Notably, knockdown of LRIG1 in organoids diminished the growth-suppressive effect of LDN193189. Furthermore, in CRC organoids, which are susceptible to growth suppression by LDN193189, simultaneous treatment with LDN193189 and trametinib, an FDA-approved MEK inhibitor, resulted in cooperative growth inhibition both in vitro and in vivo. Taken together, the simultaneous inhibition of BMP and MEK could be a novel treatment option in CRC cases, and evaluating in vitro growth suppression and LRIG1 induction by BMP inhibition using patient-derived organoids could offer functional biomarkers for predicting potential responders to this regimen.

Comparison of clinical outcome and repair integrity after arthroscopic suture-bridge and triple-row rotator cuff repairs of Fosbury flop tears.

BACKGROUND: The Fosbury flop tear (FFT) has recently been described as a rotator cuff tear that has flipped upon itself and adhered medially. FFT is known to have a high retear rate after arthroscopic rotator cuff repair. The cause of the high postoperative retear rate after arthroscopic rotator cuff repair is believed to be due to the inability to achieve anatomical reduction because of difficulties in reducing the torn tendon stump. Arthroscopic rotator cuff repairs using the triple-row technique may allow better anatomical reduction of the cuff tear when compared with the suture-bridge technique. We compared the clinical outcomes and cuff integrity of the triple-row and suture-bridge techniques in arthroscopic rotator cuff repair for FFT. METHODS: Patients with small-to-medium sized cuff tears of the supraspinatus tendon alone who were diagnosed with FFT, underwent arthroscopic rotator cuff repair, and had 2 or more years of follow-up were included. A total of 34 shoulders underwent the triple-row technique and 22 shoulders underwent the suture-bridge technique. The following were compared between the two techniques: patient background, operation time, number of anchors used during the operation, Japanese Orthopedic Association (JOA) score, active range of motion, and retear rate. RESULTS: No significant difference in patient background was found between the two techniques. Although active range of motion was significantly improved compared with preoperative scores, no significant difference was observed between techniques. The triple-row technique demonstrated a significantly higher 24-month postoperative JOA score, significantly shorter surgery time, significantly lower retear rate, and significantly larger number of anchors used during the operation. CONCLUSIONS: The triple-row technique was an effective method compared with the suture-bridge technique in cases with FFT.

Nucleobindin-2 Mediates Transforming Growth Factor-ß1-Driven Phenotypes in Zinc Finger E-Box Binding Homeobox 1-High Uterine Carcinosarcoma.

Epithelial-mesenchymal transition is a hallmark of uterine carcinosarcoma (UCS). Here, shotgun proteomics analysis used to identify biomarkers associated with blebbistatin-mediated epithelial-mesenchymal transition in UCS indicated up-regulation of nucleobindin-2 (NUCB2) in endometrial carcinoma (Em Ca) cells. Expression of N-cadherin, Snail, Slug, and ZEB1 was reduced in NUCB2 knockout Em Ca cells, whereas ZEB1, Twist1, and vimentin were up-regulated in NUCB2-overexpressing Em Ca cells. NUCB2 knockout reduced cell proliferation and migration, whereas NUCB2 overexpression had the opposite effect. Treatment of Em Ca cells with transforming growth factor (TGF)-ß1 dramatically altered morphology toward a fibroblastic appearance; concomitantly, expression of NUCB2 and ZEB1 increased. The NUCB2 promoter was also activated by transfection of Smad2. In UCS tissues, NUCB2 expression was significantly higher in sarcomatous compared with carcinomatous components, which was consistent with increased TGF-ß1 mRNA expression in stromal and sarcomatous components compared with carcinomatous components. In addition, NUCB2 score correlated positively with ZEB1 and vimentin scores, whereas ZEB1 score correlated positively with Slug and vimentin scores and inversely with the E-cadherin score. Collectively, these data indicate that TGF-ß-dependent up-regulation of NUCB2 and ZEB1 contributes to the phenotypic characteristics of sarcomatous components in UCS.

Pregnancy in MuSK-positive myasthenia gravis: A single-center case series.

INTRODUCTION/AIMS: Myasthenia gravis (MG) with muscle-specific tyrosine kinase (MuSK) antibodies (MMG) is predominantly seen in women of childbearing age. Our objective in this study was to describe the course of MMG during pregnancy and within 6 months postpartum, and to document any effect on fetal health. METHODS: A retrospective review was performed of medical records of patients with MMG seen in the Duke Myasthenia Gravis Clinic from 2003 to 2022. MMG patients with onset of MMG symptoms before or during pregnancy as well as within 6 months postpartum were reviewed. RESULTS: A total of 14 pregnancies in 10 patients were included in our study cohort. Initial MG symptoms developed during pregnancy or within 6 months postpartum in six patients. Four patients had two pregnancies, three of whom developed MG during their first pregnancy. In the patients diagnosed before pregnancy, MG symptoms increased in five of eight patients during pregnancy or postpartum. Four patients required rescue therapy with plasma exchange or intravenous immunoglobulin during pregnancy or postpartum. One patient had a cesarean section after prolonged labor due to failure of progression. There were no other complications of pregnancy or delivery, and all infants were healthy at delivery. DISCUSSION: As in non-MuSK MG, women with MMG may also have worsening or may develop initial MG symptoms during pregnancy or within 6 months postpartum. More aggressive medical therapy may be required for pregnant patients with MMG. Further study is needed to identify the mechanism and risk of worsening of MMG during pregnancy or postpartum.

Usefulness of blood biomarkers for predicting venous thromboembolism in Japanese patients with cancer.

Prospective studies on risk factors for the occurrence of venous thromboembolism (VTE) in Asian patients with cancer are limited. Therefore, the present study assessed risk factors for VTE, including multiple blood biomarkers and risk scores consisting of several risk factors, in Japanese patients receiving anticancer drug therapy. In this single-center, prospective, observational study, 200 patients with six types of cancer were enrolled and followed for 1 year to observe the occurrence of symptomatic or asymptomatic VTE. The present study evaluated risk factors, Khorana and Vienna cancer and thrombosis study (CATS) scores at enrollment, and longitudinal data on various blood biomarkers. A Vienna CATS score of ≥3 was significantly associated with VTE occurrence (HR, 2.8; 95% CI, 0.9-8.7; P=0.045). In multivariable analysis, there was a significant association between VTE and the presence of pancreatic cancer (HR, 3.2; 95% CI, 1.1-8.8; P=0.028) and high soluble fibrin (HR, 3.7; 95% CI, 1.1-7.8; P=0.036). Covariate analysis using the propensity score also showed a significant association with hemoglobin dichotomized at <100 g/l (HR, 3.9; 95% CI, 1.1-14.0; P=0.034). Longitudinal data indicated that VTE was associated with soluble fibrin baseline values and an increase in D-dimer levels over time. The present results suggested that blood biomarkers are beneficial for predicting the risk of VTE in Japanese patients with cancer. The present study also provided novel evidence for the importance of measuring soluble fibrin in patients with cancer.

Anti-cancer effect of afatinib, dual inhibitor of HER2 and EGFR, on novel mutation HER2 E401G in models of patient-derived cancer.

BACKGROUND: Precision medicine with gene panel testing based on next-generation sequencing for patients with cancer is being used increasingly in clinical practice. HER2, which encodes the human epidermal growth factor receptor 2 (HER2), is a potentially important driver gene. However, therapeutic strategies aimed at mutations in the HER2 extracellular domain have not been clarified. We therefore investigated the effect of EGFR co-targeted therapy with HER2 on patient-derived cancer models with the HER2 extracellular domain mutation E401G, based on our previous findings that this mutation has an epidermal growth factor receptor (EGFR)-mediated activation mechanism. METHODS: We generated a xenograft (PDX) and a cancer tissue-originated spheroid (CTOS) from a patient's cancer containing an amplified HER2 E401G mutation. With these platforms, we compared the efficacy of afatinib, a tyrosine kinase inhibitor having anti-HER2 and anti-EGFR activity, with two other therapeutic options: lapatinib, which has similar properties but weaker EGFR inhibition, and trastuzumab plus pertuzumab, for which evidence exists of treatment efficacy against cancers with wild-type HER2 amplification. Similar experiments were also performed with H2170, a cell line with wild-type HER2 amplification, to contrast the characteristics of these drug's efficacies against HER2 E401G. RESULTS: We confirmed that PDX and CTOS retained morphological and immunohistochemical characteristics and HER2 gene profiles of the original tumor. In both PDX and CTOS, afatinib reduced tumor size more than lapatinib or trastuzumab plus pertuzumab. In addition, afatinib treatment resulted in a statistically significant reduction in HER2 copy number at the end of treatment. On the other hand, in H2170 xenografts with wild-type HER2 amplification, trastuzumab plus pertuzumab was most effective. CONCLUSIONS: Afatinib, a dual inhibitor of HER2 and EGFR, showed a promising effect on cancers with amplified HER2 E401G, which have an EGFR-mediated activation mechanism. Analysis of the activation mechanisms of mutations and development of therapeutic strategies based on those mechanisms are critical in precision medicine for cancer patients.

Return to sports after arthroscopic Bankart repair in teenage athletes: a retrospective cohort study.

BACKGROUND: Anterior shoulder instability is frequent among young athletes. Surgical treatment for this injury aims to facilitate an early return to sports (RTS). However, the rate of recurrent instability after surgery is reportedly high among young patients, and it is unclear whether surgery ensures satisfactory RTS. The purpose of this study was to verify the clinical outcomes and RTS after arthroscopic Bankart repair in competitive teenage athletes without critical bone loss in the glenoid. METHODS: We retrospectively reviewed competitive teenage athletes who underwent arthroscopic Bankart repair. Patients with large bony defects in the glenoid, larger than 20% of the healthy side, were excluded. Clinical outcomes, recurrent instability, the final level of RTS, and the time needed for RTS were analyzed. RESULTS: In total, 50 patients with a mean follow-up period of 44.5 ± 19.6 (range, 24-85 months) months were included. The mean age at surgery was 16.8 ± 1.7 (range, 13-19 years) years. Two patients (4.0%) experienced recurrent instability. All patients returned to sports, 96% of patients participated competitively, and 76% achieved a complete return to the pre-injury level without any complaints. The time for RTS was 6.6 ± 2.7 months (range, 3-18 months), to competitions was 9.3 ± 4.0 (range, 6-24 months) months, and to complete return was 10.6 ± 4.3 (range, 8-24 months) months. The complete return rates varied by sports type, with 82% in contact athletes, 59% in dominant-hand overhead athletes, and 100% in other athletes (P = 0.026). Other preoperative factors or concomitant lesion such as bony Bankart, superior labrum tear, or humeral avulsion of glenohumeral ligament lesion did not affect the complete RTS. CONCLUSION: Arthroscopic Bankart repair is an effective surgical procedure for anterior shoulder instability, even among competitive teenage athletes. Sports type was the only factor associated with complete RTS after surgery.

Tranexamic acid administration for arthroscopic rotator cuff repair: A prospective, double-blind, randomized controlled trial.

BACKGROUND: The purpose of this study was to compare the efficacy of tranexamic acid versus placebo after arthroscopic rotator cuff repair. METHODS: This prospective, double-blind, and randomized study involved 66 patients who consecutively underwent arthroscopic rotator cuff repair from 2020 to 2021 at our hospital. Thirty-three shoulders each were randomly assigned to the tranexamic acid and control groups. In the former group, 1000 mg of tranexamic acid (20 mL) was administered intravenously 10 min before surgery and the same volume of normal saline (20 mL) was administered intravenously in the control group. We evaluated visual clarity; visual analog scale pain scores at rest, during activity, and at night; the circumference and diameter of the shoulder joint in the groups before and after the surgery at 1, 2, and 3 days, and 1 week; estimated perioperative blood loss; and operative time. Visual clarity was rated using a numeric rating scale from grade 1 (poor) to grade 3 (clear) every 15 min throughout the surgery. We compared and analyzed the results between the groups. Statistical significance was set at a p-value of <0.05. RESULTS: Visual clarity was found to be significantly better in the tranexamic acid group, with a greater percentage of grade 3 visual clarity (75.6 ± 11.2% vs 68.1 ± 13.4%, p = 0.045). The visual analog scale scores at rest and at night in the control group were significantly lower than those in the tranexamic acid group for 1 week postoperatively (13.8 ± 14.8 vs 5 ± 9.3, p = 0.008, 36.1 ± 23.3 vs 19.3 ± 24, p = 0.012). The circumference and diameter of the shoulder joint, estimated perioperative blood loss, and operative time were not significantly different between the two groups. CONCLUSION: Intravenous administration of tranexamic acid is an alternative way to improve visual clarity in arthroscopic rotator cuff repair; however, there are no other significant differences compared to the administration of placebo.